Discussion:
Resistance to thyroid hormone was
first described as a clinical entity in 1967 [7]. Subsequent studies
about the molecular pathogenesis of this syndrome identified mutations
in the region of the gene that encodes the ligand-binding domain of
THRb. Interestingly, patients with mutations in THRa were not
identified until 2012 [6]. Our patient in this article was found to
have mutation in THRb same as majority of the patients described in the
literature.
Patients with RTHb may have some symptoms or signs of hypothyroidism or
hyperthyroidism, but these are variable and, when present, often
inconstant. They frequently have elevated thyroid hormones level, high
or normal TSH and goiter which suggest the importance of THRb in
feedback of hypothalamic pituitary axis [6]. In contrast, patients
with RTHa present with musculoskeletal and gastrointestinal
abnormalities. They usually have near normal thyroid function due to
lack of THRa contribution in feedback on hypothalamic pituitary axis
[8,9]. Our patient initially presented with symptoms of
hypothyroidism including weight gain and generalized fatigability in
addition to high TSH which is consistent to typical presentation found
in the literature. However, she had normal T3 and T4 which is not
usually typical in presentation of RTHb that made our initial impression
to be subclinical hypothyroidism.
To date, more than 100 THRB mutations have been reported among
RTH patients. Most mutations substitute a single amino-acid residue in
the ligand-binding domain [10]. The most unique part in our case is
found in genetic study, which confirmed that the patient is heterozygous
in THRb gene for sequence variant designatedc.1147C>T , which is predicted to result in amino
acid substitution p.Arg383Cys. this variant appears to have
been reported in French patient with thyroid hormone resistant [11].
It was also reported in another affected individual but was inherited
from apparently unaffected father [10]. Another variant affecting
the same amino acid have also been reported in patient with thyroid
hormone resistance [12].